Electron microscopy of selectively denervated canine carotid sinuses.
Selective denervation as used to characterize the nerve endings in the carotid sinus wall of the dog. Areas of dense innervation were identified by acetylcholinesterase histochemical technique and sampled for electron microscopic study following survival periods of 48 to 144 hours after selective neurectomies were done. Large varicosities, similar to previously described mechanoreceptor endings, showed signs of degeneration after transection of the sinus nerve, but not after cranial cervical ganglionectomy or section of the glossopharyngeal nerve proximal to its sensory ganglia. These were concluded to be endings of afferent neurons. Histochemical reactions at the fine structure level demonstrated such varicosities to be acetylcholinesterase positive. Smaller varicosities containing granulated synaptic vesicles degenerated after cranial cervical ganglionectomy was done. These were interpreted to be postganglionic sympathetic endings. This study represents an example where denervation, coupled with short survival periods, serves as a technique for studying selected areas of the peripheral nervous system.


Reliability of single office blood pressure measurements.
Standard operating procedures for office blood pressure measurement (OBPM) vary greatly between guidelines and studies. We aimed to compare the difference between a single OBPM and the mean of the three following measurements. Further, we studied how many patients with possible hypertension may be missed due to short-term masked hypertension (STMH) and how many might be overdiagnosed due to short-term white coat hypertension (STWCH). In this cross-sectional, single-centre trial, 1000 adult subjects were enrolled. After 5 min of rest, four sequential standard OBPMs were performed at 2 min intervals in a quiet room in sitting position. We compared the first (fBPM) to the mean of the second to fourth measurement (mBPM). STMH was defined as fBPM <140 mm Hg systolic and <90 mm Hg diastolic and mBPM systolic ≥140 mm Hg or diastolic ≥90 mm Hg. STWCH was defined as fBPM systolic ≥140 mm Hg or diastolic ≥90 mm Hg and mBPM <140 mm Hg systolic and <90 mm Hg diastolic. Complete measurements were available in 802 subjects. Between fBPM and mBPM, 662 (82.5%), 441 (55%) and 208 (25.9%) subjects showed a difference in systolic and 531 (66.2%), 247 (30.8%) and 51 (6.4%) in diastolic blood pressure (BP) values of >2 mm Hg, >5 mm Hg and >10 mm Hg, respectively. In 3.4% of initially normotensives STMH and in 34.3% of initially hypertensives, STWCH was apparent. There are significant differences between a single OBPM and the mean of consecutive BP measurements. Our study provides evidence that a single OBPM should not be the preferred method and should be discouraged in future guidelines. NCT02552030;Results.


Evaluation of Ingenol mebutate efficacy for the treatment of actinic keratosis with Antera 3D camera.
Cumulative exposure of the skin to ultraviolet radiation promotes mutation in keratinocytes and their abnormal growth led to the formation of scaly lesions, called actinic keratoses (AKs). Its incidence is growing at an emerging rate, becoming a worldwide problem especially for occupational ultraviolet (UV) rays exposure. Detectable lesions are often associated with field changes, where the surrounding skin is altered and subclinical lesions may be present. Thus, a field-directed therapy, such as topical treatment, should be preferred for the prevention of invasive cancer development. A retrospective analysis was made, evaluating the efficacy of ingenol-mebutate gel, using a novel device the 3D in vivo optical skin Imaging (Antera 3D, Miravex, Ireland). We included all patients with multiple non-hypertrophic Aks, to whom it was prescribed ingenol-mebutate gel, applied at the dosages of 0.015 for lesions in the scalp/face (for 3 consecutive days) and at the dosage of 0.05% for lesions in the trunk and/or extremities (for 2 consecutive days). A reduction of the lesions and of median hemoglobin levels, after a follow-up of 60 days, was observed in 100% of patients. Ingenol mebutate gel, the last topical molecule appeared in the Italian market showed its efficacy using Antera 3D also in terms of hemoglobin reduction. Therefore, this camera could be considered an useful tool for the identification of the area to be treated and for therapeutic follow-up.


Fluoride exposure alters Ca2+ signaling and mitochondrial function in enamel cells.
Fluoride ions are highly reactive, and their incorporation in forming dental enamel at low concentrations promotes mineralization. In contrast, excessive fluoride intake causes dental fluorosis, visually recognizable enamel defects that can increase the risk of caries. To investigate the molecular bases of dental fluorosis, we analyzed the effects of fluoride exposure in enamel cells to assess its impact on Ca2+ signaling. Primary enamel cells and an enamel cell line (LS8) exposed to fluoride showed decreased internal Ca2+ stores and store-operated Ca2+ entry (SOCE). RNA-sequencing analysis revealed changes in gene expression suggestive of endoplasmic reticulum (ER) stress in fluoride-treated LS8 cells. Fluoride exposure did not alter Ca2+ homeostasis or increase the expression of ER stress-associated genes in HEK-293 cells. In enamel cells, fluoride exposure affected the functioning of the ER-localized Ca2+ channel IP3R and the activity of the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) pump during Ca2+ refilling of the ER. Fluoride negatively affected mitochondrial respiration, elicited mitochondrial membrane depolarization, and disrupted mitochondrial morphology. Together, these data provide a potential mechanism underlying dental fluorosis.


Use of pre-hospitalization services in two population groups of injured children and adolescents in Israel.
Trauma management includes the care provided both in hospital and by emergency medical systems in the community. In many cases it is the parents who decide where to take an injured child for care, depending on the circumstances and severity of the injury, the personal characteristics of the injured or the carer and the availability and accessibility of services. To examine the use of pre-hospitalization services and reasons for their use by children and adolescents according to the injury and personal characteristics. The study group comprised 924 Israeli citizens aged 0-17 years hospitalized for injuries in six hospitals across Israel. Carers were interviewed in the hospital regarding the circumstances of the injury event, the use of pre-hospitalization services, and sociodemographic characteristics. Data on the cause and nature of the injury were obtained from the hospital records. The proportion of severe injuries (Injury Severity Score 16+) was higher in Arab children than Jewish children (15% and 9% respectively). Sixty-three percent of the Arab children and 39% of the Jewish children used community services prior to hospitalization. The odds ratio of proceeding directly to the hospital was 0.44, 95% confidence interval 0.29-0.69, for the Arab compared to the Jewish children, controlling for severity, cause and nature of the injury, sociodemographic characteristics, and the reported availability of ambulance services. More Arab than Jewish carers tended to seek care in the community for an injured child, but the effect of personal characteristics on seeking care was similar in both population groups. Issues of availability and accessibility of services may explain the differences.


Expression of PAX-5 in B Cell Hodgkin and Non Hodgkin Lymphoma
Background: B-cell malignancies including Precursor B-cell lymphoblastic lymphoma/leukemia and Hodgkin Lymphoma show a wide spectrum of B-cell differentiation from early stage B-cell precursors to mature B-cells ending in terminal differentiation to plasma cells. Pan-B-cell antigens routinely used for the diagnosis of B-cell lymphoma, include CD19, CD20, CD22 and CD79a.PAX-5 protein, also known as B-cell-specific activation protein is a B-cell-specific transcription factor; essential for commitment and functional maintenance used in the diagnosis of B cell Hodgkin and non-Hodgkin lymphoma. PAX-5 show nuclear positivity in B cell lymphomas and moderate (dim) positivity in Hodgkinlymphoma Reed Sternberg cells make this marker ideal for diagnosing B cell malignances. Objective: To determine the expression of PAX-5 in B cell Hodgkin and non-Hodgkin Lymphoma in order to improve the diagnosis of B-cell lymphomas. Methods: In this Prospective study, all the cases of B cell lymphoma diagnosed at The Aga Khan University Hospital, Karachi from July 2010 to July 2011were included. A panel of Immunohistochemical stain was performed in all cases along with additional PAX- 5 stain with appropriate controls. Results: Total 125 cases were included. Hodgkin Lymphoma (Mixed cellularity) was the commonest B-cell lymphoma subtype, 32 (25%) cases. Other common subtypes included Hodgkin lymphoma (Nodular sclerosis subtype), diffuse large B-cell lymphoma and B lymphoblastic lymphoma. Conclusion: This study demonstrates that PAX-5 is the most sensitive and reliable immuhohistochemicalmarker in the diagnosis of B cell Hodgkin and non-Hodgkin lymphoma.


Genome- and transcriptome-wide identification of trehalose-6-phosphate phosphatases (TPP) gene family and their expression patterns under abiotic stress and exogenous trehalose in soybean.
Trehalose-6-phosphate phosphatase (TPP) is an essential enzyme catalyzing trehalose synthesis, an important regulatory factor for plant development and stress response in higher plants. However, the TPP gene family in soybean has not been reported. A comprehensive analysis of the TPP gene family identified 18 GmTPPs classified into eight groups based on the phylogenetic relationships and the conservation of protein in six monocot and eudicot plants. The closely linked subfamilies had similar motifs and intron/exon numbers. Segmental duplication was the main driving force of soybean GmTPPs expansion. In addition, analysis of the cis-regulatory elements and promoter regions of GmTPPs revealed that GmTPPs regulated the response to several abiotic stresses. Moreover, RNA-seq and qRT-PCR analysis of the tissue-specific GmTPPs under different abiotic stresses revealed that most GmTPPs were associated with response to different stresses, including cold, drought, saline-alkali, and exogenous trehalose. Notably, exogenous trehalose treatment up-regulated the expression of most TPP genes under saline-alkali conditions while increasing the carbohydrate and trehalose levels and reducing reactive oxygen species (ROS) accumulation in soybean sprouts, especially in the saline-alkali tolerant genotype. Furthermore, the interaction network and miRNA target prediction revealed that GmTPPs interacted with abiotic stress response-related transcription factors. The findings in this study lay a foundation for further functional studies on TPP-based breeding to improve soybean development and stress tolerance.


The common origin and degenerative evolution of flagella in Actinobacteria.
Flagellar motility plays an important role in the environmental adaptation of bacteria and is found in more than 50% of known bacterial species. However, this important characteristic is sparsely distributed within members of the phylum Actinobacteria, which constitutes one of the largest bacterial groups. It is unclear why this important fitness organelle is absent in most actinobacterial species and the origin of flagellar genes in other species. Here, we present detailed analyses of the evolution of flagellar genes in Actinobacteria, in conjunction with the ecological distribution and cell biological features of major actinobacterial lineages, and the co-evolution of signal transduction systems. The results presented in addition to clarifying the puzzle of sporadic distribution of flagellar motility in Actinobacteria, also provide important insights into the evolution of major lineages within this phylum.


[The pre-operative nursing assessment of patients by the operating room nurses].
The objective of this survey is to verify how many São Paulo hospitals which employ operating room nurses, proceed in having pre-operative nursing assessment of patients. This procedure is essencial to assure a continuous nursing assistance and basic to patient-needs centered nursing care. Results found show that the majority of nurses although knowing about the importance of the procedure, do not implement it.


All-Hydrocarbon Stapled Peptide Multifunctional Agonists at Opioid and Neuropeptide FF Receptors: Highly Potent, Long-Lasting Brain Permeant Analgesics with Diminished Side Effects.
Our previous study reported the multifunctional agonist for opioid and neuropeptide FF receptors DN-9, along with its cyclic peptide analogues c[D-Cys2, Cys5]-DN-9 and c[D-Lys2, Asp5]-DN-9. These analogues demonstrated potent antinociceptive effects with reduced opioid-related side effects. To develop more stable and effective analgesics, we designed, synthesized, and evaluated seven hydrocarbon-stapled cyclic peptides based on DN-9. In vitro calcium mobilization assays revealed that most of the stapled peptides, except 3, displayed multifunctional agonistic activities at opioid and neuropeptide FF receptors. Subcutaneous administration of all stapled peptides resulted in effective and long-lasting antinociceptive activities lasting up to 360 min. Among these stapled peptides, 1a and 1b emerged as the optimized compounds, producing potent central antinociception following subcutaneous, intracerebroventricular, and oral administrations. Additionally, subcutaneous administration of 1a and 1b caused nontolerance antinociception, with limited occurrence of constipation and addiction. Furthermore, 1a was selected as the final optimized compound due to its wider safety window compared to 1b.


Fast 3D chemical exchange saturation transfer (CEST) imaging of the human brain.
Chemical exchange saturation transfer magnetic resonance imaging can detect low-concentration compounds with exchangeable protons through saturation transfer to water. This technique is generally slow, as it requires acquisition of saturation images at multiple frequencies. In addition, multislice imaging is complicated by saturation effects differing from slice to slice because of relaxation losses. In this study, a fast three-dimensional chemical exchange saturation transfer imaging sequence is presented that allows whole-brain coverage for a frequency-dependent saturation spectrum (z-spectrum, 26 frequencies) in less than 10 min. The approach employs a three-dimensional gradient- and spin-echo readout using a prototype 32-channel phased-array coil, combined with two-dimensional sensitivity encoding accelerations. Results from a homogenous protein-containing phantom at 3T show that the sequence produced a uniform contrast across all slices. To show translational feasibility, scans were also performed on five healthy human subjects. Results for chemical exchange saturation transfer images at 3.5 ppm downfield of the water resonance, so-called amide proton transfer images, show that lipid signals are sufficiently suppressed and artifacts caused by B(0) inhomogeneity can be removed in postprocessing. The scan time and image quality of these in vivo results show that three-dimensional chemical exchange saturation transfer MRI using gradient- and spin-echo acquisition is feasible for whole-brain chemical exchange saturation transfer studies at 3T in a clinical time frame.


Synergistic Effects of a Calcium Phosphate/Fibronectin Coating on the Adhesion of Periodontal Ligament Stem Cells Onto Decellularized Dental Root Surfaces.
This study aimed to enhance the attachment of periodontal ligament stem cells (PDLSCs) onto the decellularized dental root surface using surface coating with fibronectin and/or calcium phosphate (CaP) and to evaluate the activity of PDLSCs attached to a coated dental root surface following tooth replantation. PDLSCs were isolated from five dogs, and the other dental roots were used as a scaffold for carrying PDLSCs and then assigned to one of four groups according to whether their surface was coated with CaP, fibronectin, CaP/fibronectin, or left uncoated (control). Fibronectin increased the adhesion of PDLSCs onto dental root surfaces compared to both the control and CaP-coated groups, and simultaneous surface coating with CaP and fibronectin significantly accelerated and increased PDLSC adhesion compared to the fibronectin-only group. On in vivo tooth replantation, functionally oriented periodontal new attachment was observed on the CaP/fibronectin-coated dental roots to which autologous PDLSCs had adhered, while in the control condition, dental root replantation was associated only with root resorption and ankylosis along the entire root length. CaP and fibronectin synergistically enhanced the attachment of PDLSCs onto dental root surfaces, and autologous PDLSCs could produce de novo periodontal new attachment in an experimental in vivo model.


Vanilla odor promotes oral feeding in premature infants-A randomized controlled trial.
Introducing early oral feeding in premature infants is important because it supports intestinal maturation and helps prevent infections. In addition, early oral feeding is likely to contribute to improved neurocognitive outcomes in preterm infants. Several holistic therapeutic strategies have been developed to improve feeding skills, food tolerance, and the ability to drink independently, including practices such as early breastfeeding, oral stimulation, and subsequent olfactory stimulation. Based on several studies using olfactory stimulation with food odors (vanilla, breast milk) to promote oral feeding in preterm infants this study was conducted to test the following hypothesis: Does olfactory stimulation with vanilla or milk odor (breast milk or formula) lead to a reduction in the time required for nasogastric tube weaning in premature infants older than 26 + 6 weeks of gestational age? In addition, does it influence secondary outcomes such as length of hospital stay, weight development, and attainment of greater amounts of independently consumed food? Premature with complete or partial feeding by gastric tube and without ventilation were included. For this study, 207 infants over 26 + 6 gestational weeks were randomized into three different study groups. Before each feeding, an olfactory presentation was made with milk odor, a vanilla Sniffin' Stick, or a control stick. In the final analysis, 165 infants were included (87 males, 78 females). At the time of randomization, infants were on average 12 ± 9.5 days old. While the influence of vanilla and milk odor did not provide a significant difference from the control for the primary outcome, a secondary analysis showed a significant group difference in the cumulative amount of independently drunk food consumed in the first ten days was the highest amount in the vanilla group. This time period was chosen due to the high dropout rate after the first ten days. In addition, there was a promising significance for earlier hospital discharge for prematurely below 32 weeks of gestation receiving vanilla odor stimulation in comparison to milk odor stimulation. Although the primary outcome of this study (gastric tube removal) did not provide significant results, a significant benefit of vanilla olfactory stimulation for preterm infants was demonstrated in subgroup analysis above milk odor stimulation. Younger preterm infants seem to benefit from the stimulation.


Motivational Climate in Youth Football Players.
(1) Background: In recent decades, the psychology of sport has gained special relevance in this field, due to the influence of psychological variables on sports performance and the regularity of sports practice. The aim of this research is to analyse the motivational climate of footballers. (2) Methods: This study uses a descriptive cross-sectional design on a sample of 156 adolescent football players, using an ad-hoc questionnaire for the recording of socio-demographic variables and the PMCSQ-2 questionnaire on motivational climate in sport. (3) Results: The results of the present investigation indicate that footballers are more oriented towards task than ego, sportsmen who compete in Honor Division being the those who are more oriented towards ego and those of National Division being more oriented towards task. (4) Conclusions: The main conclusion of this research is those who are the motivational climate is related to the division in which the players compete.


[Cardiac arrhythmia in cardiac embolism].
To study cardiac arrhythmia in patients with cardiocerebral embolism, we examined 330 patients with ischemic stroke using ECG and Holter monitoring. 33 patients were control. Group 1 consisted of 104(31.5%) patients with cardioembolic stroke, group 2--of 226(68.5%) patients with other pathogenetic stroke subtypes. Number of patients with rare and frequent supra- and ventricular extrasystole in groups 1 and 2 was not essentially different. Paroxysms of supra- and ventricular tachycardia, variants of sick sinus syndrome (SSS) and transitory atrioventricular block (AV block) of the second and third degree were identified with comparable frequency in groups 1 and 2 (0.9 to 5.8% patients). Paroxysmal atrial fibrillation (AF) was registered in 31.8% of group 1 patients and 15.9% of group 2 patients. Permanent AF occurred in 31.8 and 7.5% patients of groups 1 and 2, respectively (p < 0.00001). Thus, cardiocerebral embolism is observed most frequently in paroxysmal and permanent forms of AF. Variants of extrasystole, paroxysmal supra- and ventricular tachycardia, SSS and AV-block are not associated with embolic complications.


Still Birth classification: Application of Relevant Condition at Death (ReCoDe) classification system in a tertiary care hospital of Pakistan.
To determine the cause of stillbirth after application of relevant condition at death (ReCoDe) classification system. This was a retrospective cross sectional study of 207 women diagnosed with stillbirth after 24 completed weeks of pregnancy at the Aga Khan University Hospital (AKUH), Karachi between 1st January 2015 and 31st December 2019. The primary objective was to find the cause of stillbirth according to the new classification of relevant condition at death (ReCoDe). There were a total of 32413 live births and 207 stillbirths during the study period thus stillbirth rate of 6 per 1000 live births. In this study, 80% of women were in the age group of 20-35 years, 16% had advanced maternal age while 3.8% of women accounted for less than 20 years. Among the maternal factors; 54.5% cases were booked and the remaining were were un-booked cases. Pre-eclampsia was the most common associated maternal condition (14.9%).Fetal cause accounted for 34.7% of stillbirths and the fetal growth restriction (FGR) was the most common; 23.6%. After application of ReCoDe classification, in 81% of stillbirth cases associated condition were found and only 18.8% of cases were categorized unexplained. Application of ReCoDe classification is easy to understand and applicable, especially in low resource settings with associated causes identified in vast majority of cases.


Trends and targets in antiviral phototherapy.
Photodynamic therapy (PDT) is a well-established treatment option in the treatment of certain cancerous and pre-cancerous lesions. Though best-known for its application in tumor therapy, historically the photodynamic effect was first demonstrated against bacteria at the beginning of the 20th century. Today, in light of spreading antibiotic resistance and the rise of new infections, this photodynamic inactivation (PDI) of microbes, such as bacteria, fungi, and viruses, is gaining considerable attention. This review focuses on the PDI of viruses as an alternative treatment in antiviral therapy, but also as a means of viral decontamination, covering mainly the literature of the last decade. The PDI of viruses shares the general action mechanism of photodynamic applications: the irradiation of a dye with light and the subsequent generation of reactive oxygen species (ROS) which are the effective phototoxic agents damaging virus targets by reacting with viral nucleic acids, lipids and proteins. Interestingly, a light-independent antiviral activity has also been found for some of these dyes. This review covers the compound classes employed in the PDI of viruses and their various areas of use. In the medical area, currently two fields stand out in which the PDI of viruses has found broader application: the purification of blood products and the treatment of human papilloma virus manifestations. However, the PDI of viruses has also found interest in such diverse areas as water and surface decontamination, and biosafety.


Adipocyte-Specific Modulation of KLF14 Expression in Mice Leads to Sex-Dependent Impacts on Adiposity and Lipid Metabolism.
Genome-wide association studies identified single nucleotide polymorphisms on chromosome 7 upstream of KLF14 to be associated with metabolic syndrome traits and increased risk for type 2 diabetes (T2D). The associations were more significant in women than in men. The risk allele carriers expressed lower levels of the transcription factor KLF14 in adipose tissues than nonrisk allele carriers. To investigate how adipocyte KLF14 regulates metabolic traits in a sex-dependent manner, we characterized high-fat diet-fed male and female mice with adipocyte-specific Klf14 deletion or overexpression. Klf14 deletion resulted in increased fat mass in female mice and decreased fat mass in male mice. Female Klf14-deficient mice had overall smaller adipocytes in subcutaneous fat depots but larger adipocytes in parametrial depots, indicating a shift in lipid storage from subcutaneous to visceral fat depots. They had reduced metabolic rates and increased respiratory exchange ratios consistent with increased use of carbohydrates as an energy source. Fasting- and isoproterenol-induced adipocyte lipolysis was defective in female Klf14-deficient mice, and concomitantly, adipocyte triglycerides lipase mRNA levels were downregulated. Female Klf14-deficient mice cleared blood triglyceride and nonesterified fatty acid less efficiently than wild-type. Finally, adipocyte-specific overexpression of Klf14 resulted in lower total body fat in female but not male mice. Taken together, consistent with human studies, adipocyte KLF14 deficiency in female but not in male mice causes increased adiposity and redistribution of lipid storage from subcutaneous to visceral adipose tissues. Increasing KLF14 abundance in adipocytes of females with obesity and T2D may provide a novel treatment option to alleviate metabolic abnormalities.


Effective interactive engagement strategies for MOOC forum discussion: A self-efficacy perspective.
This mixed methods sequential explanatory study identified and explained the features of engagement strategies for MOOC forum discussion that help low-achieving students make significant progress. Triangulated data were collected from MOOC learners' (n = 335) scores in two reading assessments, their posts to the embedded online discussion forum, and their self-reflection learning journals. Based on learning progress between pre- and post-assessment tasks, MOOC learners are divided into three groups: 1) little, 2) moderate, and 3) significant progress. According to a statistical analysis of the quantified posts, surprisingly, the low-scoring students from the pre-test who demonstrated significant progress later engaged in significantly fewer peer-peer and peer-teacher interactions in the online discussion forum. Guided by self-efficacy literature, the reflective journals of these learners suggested that 1) learner-content interactions may help them advance learning and obtain new information and linguistic knowledge from the peer-made learning materials in the discussion forum; 2) they did not share and exchange ideas and answers with their peers. Instead, they prefer learning from others' discussions and wish to get quick feedback and suggestions on their contributions to the discussion forum; and 3) peer-peer and peer-teacher interactions were proposed as two solutions to regulate their online learning experience as they lack self-discipline and time-management skills. Implications include teachers' continuous support to encourage low-achieving students to learn peer-generated content and quick feedback on their contributions to the discussion forum.


[The mechanism of action of low-intensity laser radiation].
The authors review primary mechanisms of action of low-intensity laser radiation used in physiotherapy. The hypothesis suggested by the authors allows one to compare efficacy of bioenergetic action of electromagnetic radiation varying in ranges, of therapeutic lasers, in particular. However, animal experiments have shown greater than bioenergetic action efficacy of the mechanism used by the nervous system in response to laser radiation.


Characterizing patient-oriented tools that could be packaged with guidelines to promote self-management and guideline adoption: a meta-review.
Self-management is an important component of care for patients or consumers (henceforth termed patients) with chronic conditions. Research shows that patients view guidelines as potential sources of self-management support. However, few guidelines provide such support. The primary purpose of this study was to characterize effective types of self-management interventions that could be packaged as resources in (i.e., appendices) or with guidelines (i.e., accompanying products). We conducted a meta-review of systematic reviews that evaluated self-management interventions. MEDLINE, EMBASE, and the Cochrane Library were searched from 2005 to 2014 for English language systematic reviews. Data were extracted on study characteristics, intervention (content, delivery, duration, personnel, single or multifaceted), and outcomes. Interventions were characterized by the type of component for different domains (inform, activate, collaborate). Summary statistics were used to report the characteristics, frequency, and impact of the types of self-management components. A Measurement Tool to Assess Systematic Reviews (AMSTAR) was used to assess the methodological quality of included reviews. Seventy-seven studies were included (14 low, 44 moderate, 18 high risk of bias). Reviews addressed numerous clinical topics, most frequently diabetes (23, 30 %). Fifty-four focused on single (38 educational, 16 self-directed) and 21 on multifaceted interventions. Support for collaboration with providers was the least frequently used form of self-management. Most conditions featured multiple types of self-management components. The most frequently occurring type of self-management component across all studies was lifestyle advice (72 %), followed by psychological strategies (69 %), and information about the condition (49 %). In most reviews, the intervention both informed and activated patients (57, 76 %). Among the reviews that achieved positive results, 83 % of interventions involved activation alone, 94 % in combination with information, and 95 % in combination with information and collaboration. No trends in the characteristics and impact of self-management by condition were observed. This study revealed numerous opportunities for enhancing guidelines with resources for both patients and providers to support self-management. This includes single resources that provide information and/or prompt activation. Further research is needed to more firmly establish the statistical association between the characteristics of self-management support and outcomes; and to and optimize the design of self-management resources that are included in or with guidelines, in particular, resources that prompt collaboration with providers.


Autonomous exercise game use improves metabolic control and quality of life in type 2 diabetes patients - a randomized controlled trial.
Lifestyle intervention in type 2 diabetes mellitus (T2DM) is effective but needs a special local setting and is costly. Therefore, in a randomized-controlled trial we tested the hypothesis that the autonomous use of the interactive exercise game Wii Fit Plus over a period of 12 weeks improves metabolic control, with HbA1c reduction as the primary outcome, and weight loss, reduction of cardiometabolic risk factors, physical activity and quality of life (secondary outcomes) in T2DM patients. Participants (n = 220) were randomized into an intervention and a control group. The intervention group was provided with a Wii console, a balance board and the exercise game Wii Fit Plus for 12 weeks. The control group remained under routine care and received the items 12 weeks later. At baseline and after 12 weeks (and for the control group additionally after 12 weeks of intervention) the participants' health parameters, medication, physical activity and validated questionnaires for quality of life (PAID, SF12, WHO-5, CES-D) were requested and compared in a complete case analysis using the Mann-Whitney test and the Wilcoxon signed rank test. 80% of participants completed the 12-week study. Patients in the intervention group significantly improved HbA1c (from 7.1 ± 1.3% to 6.8 ± 0.9%; -0.3 ± 1.1%; p = 0.0002) in comparison to the control group (from 6.8 ± 0.9% to 6.7 ± 0.7%; -0.1 ± 0.5%) and also significantly reduced fasting blood glucose (from 135.8 ± 38.9 mg/dl to 126.6 ± 36.6 mg/dl; p = 0.04), weight (from 97.6 ± 19.2 kg to 96.3 ± 18.7 kg; p < 0.001) and body mass index (from 34.1 ± 6.5 kg/m2 to 33.5 ± 6.5 kg/m2; p < 0.001). Daily physical activity increased significantly (p < 0.001). Diabetes-dependent impairment, mental health, subjective wellbeing and quality of life also improved significantly, and the number of patients with depression decreased. Similar improvements were seen in the control group after exercise game intervention. In this trial a low-threshold intervention with the interactive exercise game Wii Fit Plus was able to motivate T2DM patients to improve physical activity, glucometabolic control and quality of life. ClinicalTrials.gov NCT01735643.


An enzyme-linked immunosorbent assay for lactose synthase (galactosyltransferase) in serum and its application as a tumor marker in ovarian carcinoma.
This assay for lactose synthase (galactosyltransferase, EC 126.96.36.199) in serum involves two sequential incubations: serially diluted standard or sample antigen is reacted with a fixed amount of antibody; unbound antibody is then adsorbed to wells of antigen-coated microtiter plates and determined by a second antibody directed against the first antibody and coupled to phosphatase. The standard curve is linear for galactosyltransferase concentrations of 10 to 600 micrograms/L. The within-assay CV of a serum sample was 9.3% (SD 4.1%), the between-assay was 3.8% (SD 2.4%). Serum galactosyltransferase concentrations computed from three different dilutions yielded CVs of 6.5% (SD 5.7%, n = 14). We evaluated the method's accuracy by recovery analysis and by comparing enzyme activity in serum with that of purified galactosyltransferase from human milk. The normal reference interval, as estimated from data on 27 healthy blood donors, was 60-436 micrograms/L (mean 224, SD 101 micrograms/L). We applied the assay to samples of serum from ovarian carcinoma patients grouped according to tumor burden. We also determined galactosyltransferase in ascites fluid and found these values useful for diagnosis, whereas determinations in serum may serve mainly for patient monitoring.


Alopecia universalis in a patient with common variable immunodeficiency.
A 12-year-old boy with common variable immunodeficiency (CVI) who developed severe alopecia is presented. His sister also had alopecia and recurrent infections and died of lung infection at the age of 7 years. The loss of hair in both children was total; the pathology of a scalp skin biopsy specimen was typical for alopecia areata. The boy was subjected to clinical and immunologic evaluation and the results were compatible with common variable immunodeficiency.


Salmonella enterica serotype Typhimurium ShdA is an outer membrane fibronectin-binding protein that is expressed in the intestine.
The shdA gene is the only determinant known to be required for persistence of Salmonella enterica serotype Typhimurium (S. Typhimurium) in the murine caecum and for efficient and prolonged shedding of the organism with the faeces. To study the biological activity of the ShdA protein, we examined its expression and binding activity. ShdA was not detected with anti-ShdA antiserum in S. Typhimurium strain ATCC14028 grown in vitro, suggesting that this protein is not expressed under standard conditions of bacterial cultivation in the laboratory. However, in mice infected with S. Typhimurium, an immunofluorescence signal detected with anti-ShdA antiserum co-localized with that generated by anti-O4 antiserum in thin sections from the caecum. Expression of the cloned shdA gene from the T7 promoter in vitro resulted in detection of ShdA in the outer membrane of S. Typhimurium and in binding of fibronectin to the bacterial surface. Binding of purified glutathione-S-transferase (GST)-ShdA fusion protein to fibronectin was dose dependent and could be partially inhibited by preincubation with antifibronectin antibodies. GST-ShdA bound to connective tissue and the basement membrane in thin sections from the murine caecum in situ. A similar labelling pattern was produced when thin sections of the murine caecum were stained with antifibronectin antiserum. Collectively, these data demonstrate that ShdA is a surface-localized, fibronectin-binding protein whose expression is induced in vivo in the murine caecum, a tissue in which a cognate receptor of this outer membrane protein is expressed.


Semiconductor real-time quality assurance dosimetry in brachytherapy.
With the increase in complexity of brachytherapy treatments, there has been a demand for the development of sophisticated devices for delivery verification. The Centre for Medical Radiation Physics (CMRP), University of Wollongong, has demonstrated the applicability of semiconductor devices to provide cost-effective real-time quality assurance for a wide range of brachytherapy treatment modalities. Semiconductor devices have shown great promise to the future of pretreatment and in vivo quality assurance in a wide range of brachytherapy treatments, from high-dose-rate (HDR) prostate procedures to eye plaque treatments. The aim of this article is to give an insight into several semiconductor-based dosimetry instruments developed by the CMRP. Applications of these instruments are provided for breast and rectal wall in vivo dosimetry in HDR brachytherapy, urethral in vivo dosimetry in prostate low-dose-rate (LDR) brachytherapy, quality assurance of HDR brachytherapy afterloaders, HDR pretreatment plan verification, and real-time verification of LDR and HDR source dwell positions.


Copper homeostasis and cuproptosis in mitochondria.
Mitochondria serve as sites for energy production and are essential for regulating various forms of cell death induced by metal metabolism, targeted anticancer drugs, radiotherapy and immunotherapy. Cuproptosis is an autonomous form of cell death that depends on copper (Cu) and mitochondrial metabolism. Although the recent discovery of cuproptosis highlights the significance of Cu and mitochondria, there is still a lack of biological evidence and experimental verification for the underlying mechanism. We provide an overview of how Cu and cuproptosis affect mitochondrial morphology and function. Through comparison with ferroptosis, similarities and differences in mitochondrial metabolism between cuproptosis and ferroptosis have been identified. These findings provide implications for further exploration of cuproptotic mechanisms. Furthermore, we explore the correlation between cuproptosis and immunotherapy or radiosensitivity. Ultimately, we emphasize the therapeutic potential of targeting cuproptosis as a novel approach for disease treatment.


Laser-transected microtubules exhibit individuality of regrowth, however most free new ends of the microtubules are stable.
To study the possible mechanism of microtubule turnover in interphase cells, we have used the 266-nm wavelength of a short-pulsed Nd/YAG laser to transect microtubules in situ in PtK2 cells at predefined regions. The regrowth and shrinkage of the transected microtubules have been examined by staining the treated cells with antitubulin mAb at various time points after laser irradiation. The results demonstrate that microtubules grow back into the transected zones individually; neither simultaneous growth nor shrinkage of all microtubules has been observed. The half-time of replacement of laser-dissociated microtubules is observed to be approximately 10 min. On the other hand, exposure of the core of the microtubule, which is expected to consist almost completely of GDP-tubulin, by transecting the internal regions of the microtubule does not render the remaining polymer catastrophically disassembled, and most transected microtubules with free minus ends do not quickly disappear. Taken together, these results suggest that most microtubules in cultured interphase cells exhibit some properties of dynamic instability (individual regrowth or shrinkage); however, other factors in addition to the hydrolysis of GTP-tubulin need to be involved in modulating the dynamics and the stability of these cytoplasmic microtubules.


Building leadership capacity to drive sustainable water management: the evaluation of a customised program.
This paper describes a customised, six-month, leadership development program (LDP) that was designed for emerging leaders in the Australian water industry who were promoting sustainable urban water management (SUWM). It also presents results from an evaluation of the program's benefits, costs and overall 'return on investment' (ROI). The program was designed to help build emergent leadership capacity in the water industry, given strong evidence that this form of leadership plays an important role in advancing SUWM. It involved '360-degree feedback' processes, training, individual leadership development plans, and coaching sessions. Its design was informed by a review of the literature, and its content was informed by local empirical research involving effective SUWM leaders. The evaluation used a seven-tier assessment framework that examined different dimensions of the program's performance using source and methodological triangulation. The results indicate that such LDPs can produce a range of positive outcomes, such as promoting desired leadership behaviours and generating a positive ROI estimate. Specifically, the program's estimated ROI was approximately 190% after only one year. The primary conclusion is that evidence-based LDPs which are highly customised for specific types of leaders in the water industry represent a promising type of intervention to build forms of leadership capacity which are needed to successfully promote SUWM.


Lateral transport of Smoothened from the plasma membrane to the membrane of the cilium.
The function of primary cilia depends critically on the localization of specific proteins in the ciliary membrane. A major challenge in the field is to understand protein trafficking to cilia. The Hedgehog (Hh) pathway protein Smoothened (Smo), a 7-pass transmembrane protein, moves to cilia when a ligand is received. Using microscopy-based pulse-chase analysis, we find that Smo moves through a lateral transport pathway from the plasma membrane to the ciliary membrane. Lateral movement, either via diffusion or active transport, is quite distinct from currently studied pathways of ciliary protein transport in mammals, which emphasize directed trafficking of Golgi-derived vesicles to the base of the cilium. We anticipate that this alternative route will be used by other signaling proteins that function at cilia. The path taken by Smo may allow novel strategies for modulation of Hh signaling in cancer and regeneration.


Flexible hemispheric microarrays of highly pressure-sensitive sensors based on breath figure method.
Recently, flexible pressure sensors featuring high sensitivity, broad sensing range and real-time detection have aroused great attention owing to their crucial role in the development of artificial intelligent devices and healthcare systems. Herein, highly sensitive pressure sensors based on hemisphere-microarray flexible substrates are fabricated via inversely templating honeycomb structures deriving from a facile and static breath figure process. The interlocked and subtle microstructures greatly improve the sensing characteristics and compressibility of the as-prepared pressure sensor, endowing it a sensitivity as high as 196 kPa-1 and a wide pressure sensing range (0-100 kPa), as well as other superior performance, including a lower detection limit of 0.5 Pa, fast response time (<26 ms) and high reversibility (>10 000 cycles). Based on the outstanding sensing performance, the potential capability of our pressure sensor in capturing physiological information and recognizing speech signals has been demonstrated, indicating promising application in wearable and intelligent electronics.


Deep Retinal Image Segmentation with Regularization Under Geometric Priors.
Vessel segmentation of retinal images is a key diagnostic capability in ophthalmology. This problem faces several challenges including low contrast, variable vessel size and thickness, and presence of interfering pathology such as micro-aneurysms and hemorrhages. Early approaches addressing this problem employed hand-crafted filters to capture vessel structures, accompanied by morphological post-processing. More recently, deep learning techniques have been employed with significantly enhanced segmentation accuracy. We propose a novel domain enriched deep network that consists of two components: 1) a representation network that learns geometric features specific to retinal images, and 2) a custom designed computationally efficient residual task network that utilizes the features obtained from the representation layer to perform pixel-level segmentation. The representation and task networks are jointly learned for any given training set. To obtain physically meaningful and practically effective representation filters, we propose two new constraints that are inspired by expected prior structure on these filters: 1) orientation constraint that promotes geometric diversity of curvilinear features, and 2) a data adaptive noise regularizer that penalizes false positives. Multi-scale extensions are developed to enable accurate detection of thin vessels. Experiments performed on three challenging benchmark databases under a variety of training scenarios show that the proposed prior guided deep network outperforms state of the art alternatives as measured by common evaluation metrics, while being more economical in network size and inference time.


[Therapy of male subfertility].
The possibilities of treating male subfertility are still limited. Approaches at medical therapy include stimulation of spermatogenesis at the testicular level, improvement of epididymal function (sperm maturation), influence on sperm transport and activation of sperm metabolism with improvement of sperm motility. Causal therapy has been most successful in patients with hormonal insufficiency and male adnexitis, while microsurgical reconstructive measures have yielded best results in cases of occlusion within the efferent seminal ducts. New therapeutic approaches include the use of mast cell blockers and alpha blockers as well as vitamin C/E as an antioxidative treatment to reduce reactive oxygen species. If medical or surgical therapy has failed, methods for improvement of sperm quality in vitro must be considered (swim-up technique, glass wool filtration, migration/sedimentation technique, density gradient centrifugation). In cases of severe male sterility factor, intracytoplasmic sperm injection (ICSI) has been a breakthrough in the therapy of childlessness. A further progress is the collection of spermatozoa from the epididymis (MESA = microsurgical epididymal sperm aspiration) or testis (TESE = testicular sperm extraction). Finally, pressure in terms of time and organization can now be avoided by the use of cryopreserved spermatozoa from the ejaculate, epididymis or testicular tissue so that microinjection may be planned independently of the partner. In any case, a close cooperation between gynecologist and andrologist is of utmost importance.


Outcomes Among Patients With Heart Failure With Reduced Ejection Fraction Undergoing Transcatheter Aortic Valve Replacement: Minimally Invasive Strategy Versus Conventional Strategy.
To investigate the effect of TAVR technique on in-hospital and 30-day outcomes in patients with aortic stenosis (AS) and reduced ejection fraction (EF). Patients with AS and concomitant low EF may be at risk for adverse hemodynamic effects from general anesthesia utilized in transcatheter aortic valve replacement (TAVR) via the conventional strategy (CS). These patients may be better suited for the minimally invasive strategy (MIS), which employs conscious sedation. However, data are lacking that compare MIS to CS in patients with AS and concomitant low EF. In this retrospective study, we identified all patients with low EF (<50%) undergoing transfemoral MIS-TAVR vs CS-TAVR between March 2011 and May 2018. Our primary endpoint was defined as the composite of in-hospital mortality and major periprocedural bleeding or vascular complications. Two hundred and seventy patients had EF <50%, while 154 patients had EF ≤35%. Overall, a total of 236 patients were in the MIS group and 34 were in the CS group. Baseline characteristics between the two groups were similar except for Society of Thoracic Surgeons (STS) score (MIS 8.4 ± 5.1 vs CS 11.7 ± 6.8; P<.01). There were no differences between the two groups in incidence of the primary endpoint (MIS 5.5% vs CS 8.8%; odds ratio for MIS, 0.60; 95% confidence interval, 0.16-2.23; P=.45). In patients with severe AS and reduced EF, MIS was not associated with adverse in-hospital or 30-day clinical outcomes compared with CS. In these patients, MIS may be a suitable alternative to CS without compromising clinical outcomes.


Modeling landscape-scale pathogen spillover between domesticated and wild hosts: Asian soybean rust and kudzu.
Many emerging pathogens infect both domesticated and wild host species, creating the potential for pathogen transmission between domesticated and wild populations. This common situation raises the question of whether managing negative impacts of disease on a focal host population (whether domesticated, endangered, or pest) requires management of only the domesticated host, only the wild host, or both. To evaluate the roles of domesticated and wild hosts in the dynamics of shared pathogens, we developed a spatially implicit model of a pathogen transmitted by airborne spores between two host species restricted to two different landscape patch types. As well as exploring the general dynamics and implications of the model, we fully parameterized our model for Asian soybean rust, a multihost infectious disease that emerged in the United States in 2004. The rust fungus Phakopsora pachyrhizi infects many legume species, including soybeans (Glycine max) and the nonnative invasive species kudzu (Pueraria montana var. lobata). Our model predicts that epidemics are driven by the host species that is more abundant in the landscape. In managed landscapes, this will generally be the domesticated host. However, many pathogens overwinter on a wild host, which acts as the source of initial inoculum at the start of the growing season. Our model predicts that very low local densities of infected wild hosts, surviving in landscape patches separate from the domesticated host, are sufficient to initiate epidemics in the domesticated host, such that managing epidemics by reducing wild host local density may not be feasible. In contrast, managing to reduce pathogen infection of a domesticated host can reduce disease impacts on wild host populations.


NovaSil clay does not affect the concentrations of vitamins A and E and nutrient minerals in serum samples from Ghanaians at high risk for aflatoxicosis.
To assess the potential interference of NovaSil (NS) clay with micronutrients in humans, vitamins A and E and minerals (15 nutrient and 15 non-nutrient minerals) were measured in serum samples from a 3-month intervention trial with NS. Participants (n = 177) were randomly divided into three groups that received 3.0 g NS day(-1) (high dose, HD), 1.5 g NS day(-1) (low dose, LD), or placebo (PL). Levels of vitamins A and E in serum were comparable among the three study groups at baseline, 1 month and 3 months of NS intervention. Gender-stratified non-parametric mixed-effect model analysis showed no significant effects of dose and dose-time interaction for levels of vitamins A and E. A significant time effect was detected; however, it was limited to an increase in vitamin E in the male participants over the course of the study. No significant differences were found in levels of the nutrient and non-nutrient minerals between the HD and PL groups at baseline and 3 months of NS intervention, except for strontium levels. Strontium was significantly increased (p < 0.001) in the HD group (male = 113.65 +/- 28.00 microg l(-1); female = 116.40 +/- 24.26 microg l(-1)) compared with the PL group (male = 83.55 +/- 39.90 microg l(-1); female = 90.47 +/- 25.68 microg l(-1)) following the 3-month intervention with NS. These results, combined with safety and efficacy data, confirm that NS clay is highly effective in reducing aflatoxin exposure and acts as a selective enterosorbent that does not affect the serum concentrations of important vitamins and nutrient minerals in humans.


Micron-sized [6,6]-phenyl C61 butyric acid methyl ester crystals grown by dip coating in solvent vapour atmosphere: interfaces for organic photovoltaics.
We have devised a novel dip coating procedure to form highly crystalline and macroscopic pi-conjugated architectures on solid surfaces. We have employed this approach to a technologically relevant system, i.e. the electron-acceptor [6,6]-phenyl C61 butyric acid methyl ester molecule (PCBM), which is the most commonly used electron-acceptor in organic photovoltaics. Highly ordered, hexagonal shaped crystals of PCBM, ranging between 1 to 80 mum in diameter and from 20 to 500 nm in thickness, have been grown by dip coating the substrates into a solution containing the fullerene derivative. These crystals have been found to possess a monocrystalline character, to exhibit a hexagonal symmetry and to display micron sized molecularly flat terraces. The crystals have been prepared on a wide variety of surfaces such as SiO(x), silanized SiO(x), Au, graphite, amorphous carbon-copper grids and ITO. Their multiscale characterization has been performed by atomic force microscopy (AFM), Kelvin probe force microscopy (KPFM), X-ray diffraction (XRD), optical microscopy, scanning and transmission electron microscopy (SEM, TEM).To test the stability of these electron accepting PCBM crystals, they have been coated with a complementary, electron donor hexa-peri-hexabenzocoronene (HBC) derivative by solution processing from acetone and chloroform-methanol blends. The HBC self assembles in a well-defined network of nanofibers on the PCBM substrate, and the two materials can be clearly resolved by AFM and KPFM.Due to its structural precision on the macroscopic scale, the PCBM crystals appear as ideal interface to perform fundamental photophysical studies in electron-acceptor and -donor blends, as well as workbench for unravelling the architecture vs. function relationship in organic solar cells prototypes.


Comparison of Visual Outcomes in Coats' Disease: A 20-Year Experience.
To report differences in visual acuities among patients with Coats' disease who sought treatment at a tertiary care university-based practice. Single-center retrospective cohort study. Patients with Coats' disease diagnosed clinically, angiographically, or both from 1995 through 2015. Patients were divided into 2 groups based on date of presentation: decade 1 (1995-2005) and decade 2 (2006-2015). Visual acuity (VA). Thirty-nine eyes of 39 patients were included with 19 eyes presenting in decade 1 and 20 eyes presenting in decade 2. Three patients demonstrated bilateral disease, but only the worse eye was included for analysis. Forty-seven percent of eyes in decade 1 demonstrated advanced stages of disease (stage 3B or worse) compared with 20% of eyes in decade 2. There was a trend for the mean initial presenting VA (±standard deviation) for decade 1 eyes to be worse (2.05±1.29 logarithm of the minimum angle of resolution [logMAR]) than for decade 2 eyes (1.45±0.99 logMAR; P = 0.1). From initial to final follow-up visit, mean VA also worsened for decade 1 eyes (P = 0.03), but remained stable for decade 2 eyes (P = 1.0). At the end of follow-up, there was a trend for mean VA for decade 1 eyes (2.28±1.17 logMAR) to be worse than for decade 2 eyes (1.60±1.15 logMAR; P = 0.07). Eight eyes were observed initially in decade 1 compared with 1 eye in decade 2, and only 1 of the observed eyes (in decade 2) developed painful glaucoma requiring enucleation. Decade 2 eyes had a higher average number of procedures per eye (6.5±4.9) compared with decade 1 eyes (1.4±1.7; P < 0.001). The earlier presentation of disease in decade 2 suggests improvements in disease detection over time. Furthermore, there was a trend for eyes to have better final VA in this decade. This is due to a combination of factors, including earlier presentation of disease, fewer eyes being observed without treatment, and eyes, when treated, receiving a higher number of procedures.


Internal derangement of the knee: diagnosis by arthrography, arthroscopy, and arthrotomy.
Three hundred eighty-four cases involving all patients with meniscal or anterior cruciate ligament tears were examined surgically by 16 orthopedic surgeons over two distinct 12-month periods. The incidence of both menisci (ipsilateral knee) torn was 3.9%, and the ratio of medial to lateral meniscal tears was 2.7:1. Twelve percent of cases had tears of the anterior cruciate ligament, 70% of which were found with a concomitant medial meniscus tear. Arthrography was completely accurate in 73.2% of cases, and arthroscopy was accurate in 94.9%. When clinical impression, arthrography, and arthroscopy were combined, the overall diagnostic accuracy was 96.8%.


Abnormal distal tubular sodium reabsorption during dopamine infusion in patients with essential hypertension evaluated by the lithium clearance methods.
The effects of low-dose dopamine infusion on renal hemodynamics, tubular function estimated by the lithium clearance technique and plasma levels of angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) were studied in 11 patients with essential hypertension (HT) and in 10 healthy control subjects (CS). Antihypertensive treatment was terminated at least 2 weeks prior to examination. Dopamine (2 micrograms/kg/min) was infused for two hours. Before dopamine infusion all measured parameters, but blood pressure, did not deviate significantly between the two groups, including 24 h urinary sodium excretion prior to investigation (HT: 166.9 mmol/24 h vs. CS: 183.4 mmol/24 h, medians). Dopamine infusion resulted in an exaggerated natriuresis in the HT group when compared with the CS group; sodium excretion: (HT: from 260 to 759 mumol/min vs. CS: from 255 to 432 mumol/min, p < 0.01) and fractional sodium excretion: (HT: from 1.6 to 4.2% vs. CS: from 1.6 to 2.4%, p < 0.01 median values). Distal fractional sodium reabsorption was significantly lower in the HT patients (HT: from 94.0 to 88.5% vs. CS: from 94.0 to 91.6%, p < 0.01). ANP decreased significantly only in the HT group (HT: from 4.8 to 3.5 pmol/l vs. CS: from 3.2 to 3.4 pmol/l, p < 0.01). Renal hemodynamics, blood pressure, urinary output, Ang II, Aldo, and AVP were changed to the same degree or unchanged in both groups. It is concluded that the exaggerated natriuretic response seen in patients with essential hypertension during low-dose dopamine infusion probably is due to a enhanced dopamine sensitivity mainly in the distal parts of the nephron.


Ischaemic enteritis in a patient with chronic renal failure: diagnosis and management decisions.
Ischaemic enteritis is rare in patients with chronic renal failure not on dialysis. Here we report a case of ischaemic enteritis in an 81-year-old woman with chronic renal failure secondary to hypertension (not dialysis dependent) who presented with acute onset of abdominal pain, non-bloody diarrhoea and subsequent oliguria. The abdominal CT with angiography showed diffuse segmental wall thickening and decreased perfusion of the long segment of the ileum, with decreased enhancement of the vessels that supply the distal ileum. The clinical diagnosis of ischaemic enteritis was made. The patient responded initially to total parenteral nutrition and intravenous antibiotics. After the initiation of haemodialysis, because of the oliguria, the ischaemic enteritis progressed to bowel infarction, and an open laparotomy was performed. This report illustrates some of the difficult therapeutic decisions in a patient with ischaemic enteritis and chronic renal failure.


An Evaluation of the Pedestrian Classification in a Multi-Domain Multi-Modality Setup.
The objective of this article is to study the problem of pedestrian classification across different light spectrum domains (visible and far-infrared (FIR)) and modalities (intensity, depth and motion). In recent years, there has been a number of approaches for classifying and detecting pedestrians in both FIR and visible images, but the methods are difficult to compare, because either the datasets are not publicly available or they do not offer a comparison between the two domains. Our two primary contributions are the following: (1) we propose a public dataset, named RIFIR , containing both FIR and visible images collected in an urban environment from a moving vehicle during daytime; and (2) we compare the state-of-the-art features in a multi-modality setup: intensity, depth and flow, in far-infrared over visible domains. The experiments show that features families, intensity self-similarity (ISS), local binary patterns (LBP), local gradient patterns (LGP) and histogram of oriented gradients (HOG), computed from FIR and visible domains are highly complementary, but their relative performance varies across different modalities. In our experiments, the FIR domain has proven superior to the visible one for the task of pedestrian classification, but the overall best results are obtained by a multi-domain multi-modality multi-feature fusion.


Molecular water oxidation mechanisms followed by transition metals: state of the art.
One clean alternative to fossil fuels would be to split water using sunlight. However, to achieve this goal, researchers still need to fully understand and control several key chemical reactions. One of them is the catalytic oxidation of water to molecular oxygen, which also occurs at the oxygen evolving center of photosystem II in green plants and algae. Despite its importance for biology and renewable energy, the mechanism of this reaction is not fully understood. Transition metal water oxidation catalysts in homogeneous media offer a superb platform for researchers to investigate and extract the crucial information to describe the different steps involved in this complex reaction accurately. The mechanistic information extracted at a molecular level allows researchers to understand both the factors that govern this reaction and the ones that derail the system to cause decomposition. As a result, rugged and efficient water oxidation catalysts with potential technological applications can be developed. In this Account, we discuss the current mechanistic understanding of the water oxidation reaction catalyzed by transition metals in the homogeneous phase, based on work developed in our laboratories and complemented by research from other groups. Rather than reviewing all of the catalysts described to date, we focus systematically on the several key elements and their rationale from molecules studied in homogeneous media. We organize these catalysts based on how the crucial oxygen-oxygen bond step takes place, whether via a water nucleophilic attack or via the interaction of two M-O units, rather than based on the nuclearity of the water oxidation catalysts. Furthermore we have used DFT methodology to characterize key intermediates and transition states. The combination of both theory and experiments has allowed us to get a complete view of the water oxidation cycle for the different catalysts studied. Finally, we also describe the various deactivation pathways for these catalysts.


Absence of testicular protection by a gonadotropin-releasing hormone analogue against cyclophosphamide-induced testicular cytotoxicity in the mouse.
Protection of testicular integrity against damage from cyclophosphamide (CY) by simultaneous treatment with a gonadotropin-releasing hormone (GnRH) analogue was reported in BALB/c mice (L.M. Glode et al., Lancet, 1: 1132-1134, 1981). This approach has been used as the basis for clinical trials in various treatment centers (D. H. Johnson et al., Blood, 65:832-836, 1985) in an attempt to prevent iatrogenic sterility in males. This study aims at duplicating the original findings and obtaining quantitative data on spermatogonial killing by CY, and possible protection by GnRH, of differentiating and stem cell spermatogonia. Mice were treated with 23 daily injections of 0.4 micrograms D-leucine-6 GnRH, and with 200 mg/kg CY on Days 8, 15, and 22. Three additional groups of mice received phosphate-buffered saline and bovine serum albumin only, GnRH only, and CY only. Animals were killed at 29 days after the last injection to determine the number of late spermatids in testicular homogenates, and at 56 days for histological measurement of the ratio of elongated spermatids to Sertoli cells in the tubules. The twenty-ninth day assay was a measure of damage to differentiating spermatogonia, whose killing results in temporary sterility. The fifty-sixth day point assay assessed damage to stem spermatogonia, whose killing results in long-term or permanent sterility. Sperm counts at 29 days were identical in saline-treated control mice and GnRH-treated mice; no sperm were present in the CY-treated mice, both with and without GnRH. Thus, killing of differentiating spermatogonia by CY is not prevented by GnRH treatment. Similarly, counts of spermatids at 56 days showed no difference between saline- and GnRH-treated groups; a reduction to approximately 40% of control counts was observed equally with CY and CY plus GnRH treatments. Since GnRH treatment did not alter spermatogonial kinetics in BALB/c mice, it is not surprising that it did not protect against CY-induced damage. Thus, the mouse is not a suitable model for analyzing such effects of GnRH on spermatogenesis, and further studies in other experimental animals are needed if they are to be used as a rationale for clinical administration of GnRH to cancer patients.


Irritable bowel syndrome is more common in women regardless of the menstrual phase: a Rome II-based survey.
Functional gastrointestinal disorders are more common in women in relation to the fluctuations of female sex hormones. We tried to know the gender-related differences in the prevalence of irritable bowel syndrome and gastrointestinal symptoms according to the menstrual phase. A total of 253 women before menopause and 252 men below age 50 were examined by a gastroenterologist after completing the questionnaire. Blood tests, endoscopic procedures, and imaging studies were done, if needed. Women were subclassified into three groups according to their menstruation period; menstrual phase, proliferative phase, and secretory phase. Finally, 179 men and 193 women were analyzed. Irritable bowel syndrome was more frequently noticed in women than in men (p=0.01). The diarrhea-dominant type was more common in men, while constipation-dominant or alternating types were more common in women (p<0.001). Of 193 women, there was no significant difference in their gastrointestinal symptoms according to their menstrual phase. Regardless of the menstrual phase, gastrointestinal symptoms are more frequent in women. Physicians should consider different symptomatic manifestations between men and women should be considered when evaluating functional gastrointestinal disorders.


Acute Effects of Static Stretching of Hamstring on Performance and Anterior Cruciate Ligament Injury Risk During Stop-Jump and Cutting Tasks in Female Athletes.
Ruan, M, Zhang, Q, and Wu, X. Acute effects of static stretching of hamstring on performance and anterior cruciate ligament injury risk during stop-jump and cutting tasks in female athletes. J Strength Cond Res 31(5): 1241-1250, 2017-There is limited research investigating antagonist stretch. The purpose of this study was to evaluate the influence of static stretching of hamstrings (SSH) on performance and anterior cruciate ligament (ACL) injury risk during stop-jump and 180° cutting tasks. Twelve female college athletes (age 20.8 ± 0.7 years; height 1.61 ± 0.05 m; mass 54.25 ± 4.22 kg) participated in this study. Subjects performed stop-jump and 180° cutting tasks under 2 conditions: after warm-up with 4 × 30 seconds SSH or after warm-up without SSH. Three-dimensional kinematic and kinetic data as well as electromyography of biceps femoris, rectus femoris, vastus medialis, and gastrocnemius medialis were collected during testing. Static stretching of hamstrings significantly enhanced jump height by 5.1% (p = 0.009) but did not change the takeoff speed of cutting. No significant changes in peak knee adduction moment or peak anterior tibia shear force were observed with SSH regardless of the task. The peak lateral tibia shear force during cutting was significantly (p = 0.036) reduced with SSH. The co-contraction of hamstring and quadriceps during the preactivation (stop-jump: p = 0.04; cutting: p = 0.05) and downward phases (stop-jump: p = 0.04; cutting: p = 0.05) was significantly reduced after SSH regardless of the task. The results suggest that SSH enhanced the performance of stop-jump because of decreased co-contraction of hamstring and quadriceps but did not change the performance of cutting. In addition, SSH did not increase ACL injury risk during stop-jump and cutting tasks and even reduced medial-lateral knee loading during cutting.


Motor skills of children newly diagnosed with Attention Deficit Hyperactivity Disorder prior to and following treatment with stimulant medication.
Motor difficulties are common in children with Attention Deficit Hyperactivity Disorder (ADHD). Although preliminary evidence has suggested that methylphenidate can improve the motor skills in children with ADHD and Developmental Coordination Disorder (DCD), the effect of stimulant medication on motor performance in children newly diagnosed with ADHD with or without motor impairment remains unclear. A cohort study of 49 medication-naïve children (39 male; mean age 8.4±1.3 years) with ADHD was conducted. Children were evaluated using the Movement Assessment Battery for Children and the developmental test of visual motor integration at diagnosis and again three months following daily treatment with a stimulant medication. Motor difficulties were highly present at baseline (73.5%) but resolved in a subset after treatment with stimulant medication, suggesting that their motor difficulties may be attributed in part to their attentional problems. Nevertheless, motor impairment persisted in 55.1% of the sample. The severity of the behavioural symptoms was significantly associated with balance skills in children without motor impairments (r(2)=0.30, p<0.01) and with visual motor integration skills in children with persisting motor difficulties (r(2)=0.27, p<0.01). Attentional difficulties negatively affect the motor skills of children with ADHD. Following the use of stimulant medication, an important subset continued to demonstrate motor difficulties. The improvement in behaviour was insufficient to resolve motor problems and these children should therefore be targeted for rehabilitation services.


The Influence of Spatial Configuration of Residential Area and Vector Populations on Dengue Incidence Patterns in an Individual-Level Transmission Model.
Dengue is a mosquito-borne infectious disease that is endemic in tropical and subtropical countries. Many individual-level simulation models have been developed to test hypotheses about dengue virus transmission. Often these efforts assume that human host and mosquito vector populations are randomly or uniformly distributed in the environment. Although, the movement of mosquitoes is affected by spatial configuration of buildings and mosquito populations are highly clustered in key buildings, little research has focused on the influence of the local built environment in dengue transmission models. We developed an agent-based model of dengue transmission in a village setting to test the importance of using realistic environments in individual-level models of dengue transmission. The results from one-way ANOVA analysis of simulations indicated that the differences between scenarios in terms of infection rates as well as serotype-specific dominance are statistically significant. Specifically, the infection rates in scenarios of a realistic environment are more variable than those of a synthetic spatial configuration. With respect to dengue serotype-specific cases, we found that a single dengue serotype is more often dominant in realistic environments than in synthetic environments. An agent-based approach allows a fine-scaled analysis of simulated dengue incidence patterns. The results provide a better understanding of the influence of spatial heterogeneity on dengue transmission at a local scale.


Experimental study and optimization of scan parameters that influence radiation dose in temporal bone high-resolution multidetector row CT.
MDCT has some specific scan parameters that may systematically increase or decrease radiation dose to patients. This study explored the scan protocol parameters that impact radiation dose in temporal bone MDCT and determined the optimal scan parameters that balance radiation dose with diagnostic image quality. Using exsomatized cadaveric heads, traditional axial scanning, and helical scanning were performed with different detector collimations. Helical scans of the same scan region were then acquired by using the determined optimal detector collimation and various tube voltages, whereas other scan parameters remained fixed. Next, the scans were repeated by using various tube current-time products by using the determined optimal tube voltage. Last, with fixed tube current-time product, the scans were repeated with various pitches. All thin-section, helically acquired scans were reformatted to axial and coronal images with respect to the relevant scanning baseline. In each of the image volumes, the mean and SD HU values in regions of interest were measured in the central section of the internal auditory canal, and CNR values were calculated. In agreement with theory, wider detector collimations such as 16 × 0.625 mm and 64 × 0.625 mm were associated with lower radiation doses than narrower collimations due to their lower overbeaming and higher geometric efficiency. In helical scanning, the detector collimation of 16 × 0.625 mm had higher image quality and the minimum DLP. Axial and coronal images acquired by using a 140-kVp tube voltage had significantly lower noise than scans acquired at 120 or 80 kVp with equivalent volume CT dose index. Diagnostic image quality was achieved when using a minimum tube current-time product of 120 mAs. Noise, CNR, and dose were jointly optimized with a pitch of 0.685. Temporal bone CT scanning parameters may be optimized by following a systematic procedure that allows for the optimization of diagnostic image quality and the minimization of radiation dose. One such procedure for a particular 64-section MDCT scanner has been presented.


Differential dependencies on [Ca2+] and temperature of the monolayer spontaneous curvatures of DOPE, DOPA and cardiolipin: effects of modulating the strength of the inter-headgroup repulsion.
Biomembranes assume nonlamellar structures in many cellular events, with the tendency of forming a nonlamellar structure quantified by the monolayer spontaneous curvature, C(0), and with many of these events involving the acts of Ca(2+). Despite this biologically important intimacy, how C(0) is affected by [Ca(2+)] is unknown. In this study, we use the X-ray diffraction technique and the reconstruction of electron density profiles to measure the C(0)s of a zwitterionic phospholipid, DOPE, and two anionic phospholipids, DOPA and 18 : 1 (9Z) cardiolipin, at temperatures from 20 °C to 40 °C and [Ca(2+)]s from 0 mM to 100 mM; these phospholipids are chosen to examine the contributions of the electric charge density per molecule. While showing a strong dependence on temperature, C(0,DOPE) is nearly independent of [Ca(2+)]. In contrast, C(0,DOPA) and C(0),cardiolipin are almost unresponsive to the temperature change but affected by the [Ca(2+)] variation; and C(0,DOPA) varies with [Ca(2+)] ∼1.5 times more strongly than C(0,cardiolipin), with the phase preferences of DOPA and cardiolipin shifting to the H(II) phase and remaining on the Lα phase, respectively, at [Ca(2+)] = 100 mM. From these observations, we reveal the effects of modulating the strength of the inter-headgroup repulsion and discuss the mechanisms underlying the phase behaviour and cellular functions of the investigated phospholipids. Most importantly, this study recognizes that the headgroup charge density is dominant in dictating the phase behaviour of the anionic phospholipids, and that the unique molecular characteristics of cardiolipin are critically needed both for maintaining the structural integrity of cardiolipin-rich biomembranes and for fulfilling the biological roles of the phospholipid.


A novel high accuracy model for automatic surgical workflow recognition using artificial intelligence in laparoscopic totally extraperitoneal inguinal hernia repair (TEP).
Artificial intelligence and computer vision are revolutionizing the way we perceive video analysis in minimally invasive surgery. This emerging technology has increasingly been leveraged successfully for video segmentation, documentation, education, and formative assessment. New, sophisticated platforms allow pre-determined segments chosen by surgeons to be automatically presented without the need to review entire videos. This study aimed to validate and demonstrate the accuracy of the first reported AI-based computer vision algorithm that automatically recognizes surgical steps in videos of totally extraperitoneal (TEP) inguinal hernia repair. Videos of TEP procedures were manually labeled by a team of annotators trained to identify and label surgical workflow according to six major steps. For bilateral hernias, an additional change of focus step was also included. The videos were then used to train a computer vision AI algorithm. Performance accuracy was assessed in comparison to the manual annotations. A total of 619 full-length TEP videos were analyzed: 371 were used to train the model, 93 for internal validation, and the remaining 155 as a test set to evaluate algorithm accuracy. The overall accuracy for the complete procedure was 88.8%. Per-step accuracy reached the highest value for the hernia sac reduction step (94.3%) and the lowest for the preperitoneal dissection step (72.2%). These results indicate that the novel AI model was able to provide fully automated video analysis with a high accuracy level. High-accuracy models leveraging AI to enable automation of surgical video analysis allow us to identify and monitor surgical performance, providing mathematical metrics that can be stored, evaluated, and compared. As such, the proposed model is capable of enabling data-driven insights to improve surgical quality and demonstrate best practices in TEP procedures.


Next-Generation Payment System for Device-to-Device Content and Processing Sharing.
Recent developments in telecommunication world have allowed customers to share the storage and processing capabilities of their devices by providing services through fast and reliable connections. This evolution, however, requires building an incentive system to encourage information exchange in future telecommunication networks. In this study, we propose a mechanism to share bandwidth and processing resources among subscribers using smart contracts and a blockchain-based incentive mechanism, which is used to encourage subscribers to share their resources. We demonstrate the applicability of the proposed method through two use cases: (i) exchanging multimedia data and (ii) CPU sharing. We propose a universal user-to-user and user-to-operator payment system, named TelCash, which provides a solution for current roaming problems and establishes trust in X2X communications. TelCash has a great potential in solving the charges of roaming and reputation management (reliance) problems in telecommunications sector. We also show, by using a simulation study, that encouraging D2D communication leads to a significant increase in content quality, and there is a threshold after which downloading from base station is dramatically cut down and can be kept as low as 10%.


Distribution, management and diversity of yam local varieties in Brazil: a study on Dioscorea alata L.
Widely spread in the tropics, yams were introduced into Brazil during the colonial period and are currently grown throughout the country. Despite its importance as a pharmacological and food source, there is a lack of studies describing how and where this tuber is grown in Brazil. The aim of this study was to provide an overview of the cultivation and distribution of Dioscorea alata in different Brazilian regions. A total of 63 farmers were visited in different municipalities and communities in four regions in the country: South, Southeast, Northeast and Midwest. Semi-structured interviews were conducted to collect socio-economic, use, management and diversity data for this crop. The majority of interviewers were men, married, with children, using retirement benefits and agriculture as income and family labour as the main support in the yam cultivation. A wide distribution of this species was found, with the occurrence of D. alata in the four sampled regions. A variety of vernacular names for this species was collected, differing according to the region where it is cultivated. Most farmers cultivate yams in fields, however an increased usage of home gardens for the cultivation of this tuber was found. Also, most farmers cultivate yams in association with other crops in areas of different sizes and slash and burn practices, although mostly disappearing, are still being used by many farmers. The results of this study provide more concrete data on the distribution and diversity of this important crop.


[Elective induction of labour at 39 weeks; better than expectant management in low-risk women].
The ARRIVE trial has shown that elective induction of labour at 39 weeks improves maternal and foetal outcomes in comparison with expectant management. Caesarean sections, hypertensive disorders and neonatal ventilator support were all found to be reduced after elective induction. The trial was performed in an American nulliparous low-risk population. Several American professional organizations have now adapted their recommendation on elective induction in nulliparous low-risk women. These organizations now suggest informing women about the potential benefits, and offer elective induction in a model of shared decision-making. In the Netherlands there has been some reluctance amongst professionals to address this issue. This might be related to a conservative obstetric approach and the Dutch obstetric model with its three separate levels of care. Nevertheless, this subject should be addressed in a scientific, professional and unprejudiced way, given the evidence and potential implications for the large group of low-risk women and neonates in the Netherlands.


INTRAGRO: A machine learning approach to predict future growth of trees under climate change.
The escalating impact of climate change on global terrestrial ecosystems demands a robust prediction of the trees' growth patterns and physiological adaptation for sustainable forestry and successful conservation efforts. Understanding these dynamics at an intra-annual resolution can offer deeper insights into tree responses under various future climate scenarios. However, the existing approaches to infer cambial or leaf phenological change are mainly focused on certain climatic zones (such as higher latitudes) or species with foliage discolouration during the fall season. In this study, we demonstrated a novel approach (INTRAGRO) to combine intra-annual circumference records generated by dendrometers coupled to the output of climate models to predict future tree growth at intra-annual resolution using a series of supervised and unsupervised machine learning algorithms. INTRAGRO performed well using our dataset, that is dendrometer data of P. roxburghii Sarg. from the subtropical mid-elevation belt of Nepal, with robust test statistics. Our growth prediction shows enhanced tree growth at our study site for the middle and end of the 21st century. This result is remarkable since the predicted growing season by INTRAGRO is expected to shorten due to changes in seasonal precipitation. INTRAGRO's key advantage is the opportunity to analyse changes in trees' intra-annual growth dynamics on a global scale, regardless of the investigated tree species, regional climate and geographical conditions. Such information is important to assess tree species' growth performance and physiological adaptation to growing season change under different climate scenarios.


Matrix metalloproteinases and their inhibitors in exfoliation syndrome.
The purpose of this study was to determine the expression of metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the aqueous humour of patients with exfoliation syndrome (XFS). XFS and control samples were analysed for their MMP content by zymography and for their tissue inhibitors by ELISA. In XFS eyes, an increase for up to 60% in almost all MMPs was observed, as compared to the controls. MMP-2 and MMP-9 were found to predominate. TIMP-1 levels in XFS samples were slightly decreased, while TIMP-2 levels were similar to those of the controls. Our findings suggest that MMPs may be crucial in the progression of XFS, by degrading the abnormal fibrillar matrix components in the anterior segment tissues of XFS eyes. However, the increased levels of MMPs seem not to be able to overcome the overproduction and accumulation of the exfoliative material.


Anti-CD43 monoclonal antibody L11 blocks migration of T cells to inflamed pancreatic islets and prevents development of diabetes in nonobese diabetic mice.
Nonobese diabetic mice are a well-known model for human insulin-dependent diabetes mellitus. These mice develop autoimmune-mediated inflammation of the pancreatic islets, followed by destruction of the insulin-producing beta cells and development of diabetes. Nonobese diabetic mice also have salivary gland inflammation, and serve as a model for human Sjogren's syndrome. T cells are a prominent component of the inflammatory infiltrate in these sites, and T cell recruitment from the blood is thought to be essential for the initiation and maintenance of pathologic tissue damage. A unique mAb to murine CD43, L11, has recently been shown to block the migration of T cells from blood into organized lymphoid tissues. Here we demonstrate that L11 significantly inhibits T cell migration from blood into inflamed islets and salivary glands. Treatment of nonobese diabetic mice with L11 from 1 to 4 or 8 to 12 wk of age led to significant protection against the development of diabetes. Moreover, protection was long-lived, with decreased incidence of diabetes even months after cessation of Ab administration. When treatment was started at 1 wk of age, L11 inhibited the development of inflammation in pancreatic islets and salivary glands. L11 treatment had no long-term effect on numbers or phenotypes of peripheral lymphocytes. These data indicate that anti-CD43 Abs that block T cell migration may be useful agents for the prevention or treatment of autoimmune diseases including insulin-dependent diabetes mellitus and Sjogren's syndrome.


National Patterns of Filled Prescriptions and Third-Line Treatment Utilization for Privately Insured Women With Overactive Bladder.
The aim of this study was to evaluate national patterns of care for women with overactive bladder (OAB) in an administrative data set and identify potential areas for improvement. We performed an analysis using the OptumLabs Data Warehouse, which contains deidentified administrative claims data from a large national US health insurance plan. The study included women, older than 18 years, with a new OAB diagnosis from January 1, 2007, to June 30, 2017. We excluded those with an underlying neurologic etiology, with interstitial cystitis/painful bladder syndrome, were pregnant, or did not have continuous enrollment for 12 months before and after OAB diagnosis. Trends in management were assessed via the Cochran-Armitage test. Time to discontinuation among medications was compared using t test. Of 1.4 million women in the database during the study time frame, 60,246 (4%) were included in the study. Median age was 61 years [interquartile range (IQR), 50-73], and median follow-up was 2.6 years (IQR, 1.6-4.2). Overall, 37% were treated with anticholinergics, 5% with beta-3 agonists, 7% with topical estrogen, and 2% with pelvic floor physical therapy; 26% saw a specialist; and 2% underwent third-line therapy. Median time to cessation of prescription filling was longer for beta-3 agonists versus anticholinergics [median, 4.1 months (IQR, 1-15) vs 3.6 months (IQR, 1-10); P < 0.0001]. Use of third-line therapies significantly increased over the study time frame, from 1.1% to 2.2% (P < 0.0001). Most of the patients do not continue filling prescriptions for OAB medications, and a minority of patients were referred for specialty evaluation. Although third-line therapy use is increasing, it is used in a small proportion of women with OAB. Given these patterns, there may be underutilization of specialist referral and other OAB therapies.


Triple Arterial Phase CT of the Liver with Radiation Dose Equivalent to That of Single Arterial Phase CT: Initial Experience.
Purpose To develop and evaluate a triple arterial phase CT liver protocol with a similar radiation dose to that of standard single arterial phase CT in study subjects suspected of having hepatocellular carcinoma (HCC). Materials and Methods The study consisted of a retrospective part A for protocol development (n = 15) and a prospective part B to evaluate diagnostic accuracy (n = 38). All 53 participants underwent perfusion CT with 50 mL contrast material between August 2013 and September 2014. Group B underwent an additional standard multiphasic liver CT examination with 120 mL of contrast material (range, 70-143 mL). Image sets from triple arterial phase imaging were reconstructed from perfusion CT by fusing images from three dedicated arterial time points. Triple arterial phase CT and standard single arterial phase CT were compared by two readers, who assessed subjective image quality and HCC detection rate. A third reader served as reference reader and assessed objective image quality. The paired Student t test, Wilcoxon signed rank test, jackknife alternative free-response receiver operating characteristic (JAFROC), and JAFROC curve were applied. Results The mean volume CT dose index was 11.6 mGy for triple arterial phase CT and 11.9 mGy for standard single arterial phase CT (P = .73). Triple arterial phase CT showed lower image noise and better contrast-to-noise ratio compared with standard single arterial phase CT (P < .001 and P = .032, respectively); however, there was no significant difference in lesion-to-liver-contrast ratio (P = .31). Subjective image quality was good for both protocols. The detection rate of the 65 HCC lesions was 82% for reader 1 and 83% for reader 2 at triple arterial phase CT and 80% for reader 1 and 77% for reader 2 at standard single arterial phase CT (P = .4). Conclusion Triple arterial phase imaging is feasible at the same radiation dose as that used for standard single arterial phase CT. Triple arterial phase imaging provides equivalent to superior image quality and equal HCC detection rate despite the use of less than half the contrast material dose used at standard single arterial phase CT. © RSNA, 2018.


Proliferative response of clonal acute myelogenous leukemia cells in localized grafts of normal bone marrow stroma to in vivo stimulation of myelopoiesis.
Bone marrow from inbred Wistar/Furth (W/Fu) rats, normal and 90% replaced by acute myelogenous leukemia (AML), was transplanted, respectively, to the left and right kidneys of adult W/Fu rats. After a transient period of hypocellularity, AML grafts repopulated to pre-transplant cellularity by day 9, whereas normal bone marrow (NBM) grafts required 25 days for repopulation to pre-transplant cellularity. Grafted leukemia cells remained localized to the kidney for 17 days. In NBM grafts phlebotomy accelerated erythroid proliferation, and intrathoracic inoculation of live Escherichia coli accelerated myeloid proliferation; in AML grafts only E. coli injection increased bone marrow proliferation. There was no morphologically detectable differentiation of W/Fu AML cells. These studies provide evidence of a myelopoietic response of AML blast cells in vivo and present a transplantation technique for comparison of localized grafts of leukemic and normal bone marrow in the same animal.


Factors associated with a drive for muscularity among gay and bisexual men.
Among gay and bisexual men, body dissatisfaction can manifest itself in the form of a desire for increased muscularity. Possibly in response to homophobia, the socio-sexual culture of gay and bisexual men privileges muscularity and may help to perpetuate a sense of body dissatisfaction. Little is known about factors associated with a drive for muscularity among gay and bisexual men. This study recruited participants (n = 400) at Toronto's 2008 lesbian, gay, bisexual and transgender festival to provide data used to examine the relationship between a drive for muscularity and demographics (age, race, education, HIV status), psychological factors (depression, disordered eating, internalised homophobia, substance use), body mass, a history of childhood sexual abuse and sexual risk. Multivariate analyses revealed that a drive for muscularity was associated with age, disordered eating, depression, sexual risk and internalised homonegativity. These findings can be used to advance the health and wellbeing of gay and bisexual men, particularly interventions designed to mitigate the effects of internalised homonegativity and policies aimed at reducing homophobia.


The effectiveness of exercise on improving cognitive function in older people: a systematic review.
The well-documented physical benefits of exercise and the value of exercise for improving mental health have raised the profile and role of exercise in healthcare. However, studies evaluating the effects of exercise on neurocognitive function have produced equivocal results. This study was designed to examine the effectiveness of exercise on improving cognitive function in older people. Researchers used a narrative synthesis approach in this review and conducted a computer-based search in MEDLINE, CINAHL, Cochrane Library, and Airiti Library (Chinese) from 2006 to 2009 using the search terms exercise, physical activity, and cognition. Research quality appraisal was rated using Consolidated Standards of Reporting Trials criteria. This review included 12 medium- to high-quality randomized controlled trials. Most studies examined used a 60-minute exercise regimen scheduled three times per week that was continued for 24 weeks. Of the 12 studies, 8 revealed that exercise can improve cognitive function. Five studies focused on healthy older people and three studied older people who had impaired cognition at baseline. Analysis of the studies showed simple, one-component exercise as better for older people with cognitive impairment and multicomponent exercise as better for those without such impairment. This systematic review demonstrated that an exercise regimen of 6 weeks and at least 3 times per week for 60 minutes had a positive effect on cognition. Whether multicomponent exercise is significantly more effective in improving cognitive function, particularly in healthy older people, should be tested using larger trials with more rigorous methodology.


Modeling apical and basal tree contribution to orientation selectivity in a mouse primary visual cortex layer 2/3 pyramidal cell.
Pyramidal neurons, a mainstay of cortical regions, receive a plethora of inputs from various areas onto their morphologically distinct apical and basal trees. Both trees differentially contribute to the somatic response, defining distinct anatomical and possibly functional sub-units. To elucidate the contribution of each tree to the encoding of visual stimuli at the somatic level, we modeled the response pattern of a mouse L2/3 V1 pyramidal neuron to orientation tuned synaptic input. Towards this goal, we used a morphologically detailed computational model of a single cell that replicates electrophysiological and two-photon imaging data. Our simulations predict a synergistic effect of apical and basal trees on somatic action potential generation: basal tree activity, in the form of either depolarization or dendritic spiking, is necessary for producing somatic activity, despite the fact that most somatic spikes are heavily driven by apical dendritic spikes. This model provides evidence for synergistic computations taking place in the basal and apical trees of the L2/3 V1 neuron along with mechanistic explanations for tree-specific contributions and emphasizes the potential role of predictive and attentional feedback input in these cells.